The role of WNT singling activation and its blockage in the focal retinal lesion of Ccl2-/-/Cx3cr1-/- mice with and without rd8 background

Tuesday, September 23, 2014 — Poster Session III
12:00 p.m. – 2:00 p.m.	FAES Academic Center	NEI	PHARM-4

Authors

• J Tuo
• Y Wang
• R Chen
• Y Li
• M mei
• H Qian
• D Shen
• R Pelnalva
• M Abu-Asab
• H Xu
• J Ma
• CC Chan

Abstract

The canonical Wnt signaling is activated by retinal injury. Under disease conditions, the Wnt mediates inflammatory responses. Inflammation has been detected in age-related macular degeneration (AMD) retinas and Ccl2-/-/Cx3cr1-/- (DKO) mice with or without rd8 background. We evaluated the effects of Wnt-β-catenin activation and an antibody against LRP6, the co-receptor of Wnt on these two models by injecting anti-LRP6 antibody intravitreally into the right eyes and using left eyes as controls. For DKOrd8 mice, the fundus showed a slower progression of lesions in the right eyes as compared to the left eyes. Histology confirmed the clinical observation. Light-adapted ERG of the treated eyes exhibited larger amplitudes compared to control eyes. There was a significantly lower A2E in the treated eyes compared to controls. Microarray of 92 Wnt genes expression pattern was similar in both eyes. Western blotting indicated local administration of 2F1 antibody to suppress the activation of Wnt pathway in the retina. For DKO mice, the treatment improved ERG but less effect on RPE degeneration. We conclude that the canonical Wnt signaling plays a role in the focal retina lesion of both DKOrd8 and DKO mice; and intravitreal anti-LRP6 antibody might be neuroprotective via deactivation of canonical Wnt pathway.

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